MUSCULOSKELETAL PHARMACOLOGY. A story of the inflamed

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1 MUSCULOSKELETAL PHARMACOLOGY A story of the inflamed 1

2 INFLAMMATION Pathophysiology Inflammation Reaction to tissue injury Caused by release of chemical mediators Leads to a vascular response Fluid and WBCs migrate to injured site. Chemical mediators Histamines Kinins Prostaglandins 2

3 INFLAMMATION (CONT.) Pathophysiology Chemical mediators Histamines First mediator in inflammatory process Cause dilation of arterioles Increase capillary permeability Kinins (Bradykinin) Increase capillary permeability Increase pain Prostaglandins Increase capillary permeability Increase vasodilation Increase pain and fever 3

4 INFLAMMATION (CONT.) Pathophysiology Cardinal signs of inflammation Redness Swelling Heat Pain Loss of function 4

5 INFLAMMATION (CONT.) Pathophysiology Inflammation Cyclooxygenase (COX) enzyme Converts arachidonic acid into prostaglandins Has two enzyme forms: COX-1: protects stomach lining and regulates blood platelets COX-2: triggers inflammation and pain 5

6 ANTIINFLAMMATORY DRUGS Antiinflammatory drug groups Nonsteroidal antiinflammatory drugs (NSAIDs) Corticosteroids Disease-modifying antirheumatic drugs Antigout drugs 6

7 ANTIINFLAMMATORY DRUGS (CONT.) NSAIDs Inhibit biosynthesis of prostaglandins Analgesic effect Antipyretic effect Inhibit platelet aggregation Mimic effects of corticosteroids 7

8 NSAIDS Action Inhibit COX enzyme Inhibit prostaglandin synthesis Uses Reduce inflammation and pain Not recommended for fever or headaches Except aspirin, ibuprofen 8

9 NSAIDS (CONT.) First-generation NSAIDs Salicylates Parachlorobenzoic acid Phenylacetic acids Propionic acid derivatives Fenamates Oxicams Second-generation NSAIDs COX-2 inhibitors 9

10 COX-1 AND COX-2 INHIBITORS Uses of COX-1 and COX-2 Inhibitors. 10

11 SALICYLATES Aspirin (acetylsalicylic acid) (ASA) Action Antiinflammatory, antiplatelet, antipyretic effects Therapeutic serum salicylate level 15 to 30 mg/dl Toxic serum salicylate level Greater than 30 mg/dl 11

12 SALICYLATES (CONT.) Drug-lab-food interactions Drugs Increased bleeding with anticoagulants Hypoglycemia with oral antidiabetics Increased gastric ulcer risk with glucocorticoids Lab Increase PT, bleeding time, INR, uric acid Decrease potassium, cholesterol, T 3 and T 4 levels Foods containing salicylates Prunes, raisins, licorice, certain spices 12

13 SALICYLATES (CONT.) Aspirin Caution Do not take with other NSAIDs. Avoid during third trimester of pregnancy. Do not give to children with flu or virus symptoms (Reye syndrome). Side effects/adverse reactions Tinnitus, hearing loss Dizziness, confusion, drowsiness GI distress, peptic ulcer Thrombocytopenia, leukopenia, agranulocytosis Hepatotoxicity 13

14 SALICYLATES (CONT.) Hypersensitivity Tinnitus, dizziness, bronchospasm Salicylism (mild) Tinnitus, dizziness, headache, confusion, sweating, drowsiness, thirst, nausea, vomiting, diarrhea Severe salicylate poisoning Convulsions, cardiovascular collapse, coma 14

15 PARA-CHLOROBENZOIC ACID Indomethacin (Indocin) Sulindac (Clinoril) Tolmetin (Tolectin) This group of NSAIDs may cause sodium and water retention and increased blood pressure. 15

16 PHENYLACETIC ACID DERIVATIVES Diclofenac sodium (Voltaren): indicated for rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. No antipyretic effect. Ketorolac (Toradol): inhibits prostaglandin synthesis, recommended for short-term management of pain. 16

17 PROPIONIC ACID DERIVATIVES Ibuprofen (Motrin, Advil) Fenoprofen calcium (Nalfon) Naproxen (Naprosyn) Ketoprofen (Orudis) Flurbiprofen (Ansaid) Oxaprozin (Daypro) 17

18 PROPIONIC ACID DERIVATIVES (CONT.) Ibuprofen Drug interactions Increased bleeding with warfarin, increased effects with phenytoin, sulfonamides, warfarin Decreased effect with aspirin Side effects Gastric distress (to be taken with food) Tinnitus, dizziness, confusion, edema Blood dyscrasias, dysrhythmias, nephrotoxicity 18

19 FENAMATES Meclofenamate (Meclomen) and mefenamic acid (Ponstel) Potent NSAIDs Used for acute and chronic arthritic conditions Gastric irritation is a common side effect. Patients with a history of peptic ulcer should avoid taking this group of drugs. Other side effects include edema, dizziness, tinnitus, and pruritus. 19

20 OXICAMS Piroxicam (Feldene) Indicated for long-term arthritic conditions Can cause gastric problems like ulceration and epigastric distress Well-tolerated Full clinical response in 1 to 2 weeks Should not be taken with aspirin or other NSAIDs 20

21 SELECTIVE COX-2 INHIBITORS Action Selectively inhibits COX-2 enzyme without inhibition of COX- 1 Use Decrease inflammation and pain Drug agents Celecoxib Similar agents Nabumetone (Relafen) 21

22 SELECTIVE COX-2 INHIBITORS (CONT.) Caution Avoid during third trimester of pregnancy. Side effects Headache, dizziness, sinusitis GI distress Peripheral edema NSAIDs in older adults Greater incidence of GI distress, ulceration Reduced dose decreases risk of side effects. 22

23 CORTICOSTEROIDS Prednisone, prednisolone, dexamethasone Control inflammation by suppressing or preventing many of the components of the inflammatory process at the injured site Not the drug of choice for arthritis because of their numerous side effects Frequently used to control arthritic flare-ups Taper off 23

24 GOUT Gout pathophysiology Inflammatory disease of joints, tendons, and other tissues Usually occurs in great toe Defect in purine metabolism leads to uric acid accumulation. Purine-containing foods: organ meats, sardines, salmon, gravy, herring, liver, meat soups, and alcohol (especially beer) 24

25 ANTIGOUT DRUGS Colchicine Inhibit migration of leukocytes to inflamed site Side effects GI distress Taken with food to avoid GI distress Contraindications Severe renal, cardiac, or GI problem 25

26 ANTIGOUT DRUGS (CONT.) Uric acid inhibitors Allopurinol (Zyloprim) Action Decreases production of uric acid Prophylactic to prevent gout attacks Nursing interventions Monitor CBC, liver enzymes, renal function. Tell patient to get yearly eye examinations for visual changes. Advise patient to avoid alcohol, caffeine, and thiazide diuretics that increase uric acid level. Advise patient to increase fluid intake to increase uric acid excretion. 26

27 ANTIGOUT DRUGS (CONT.) Uricosurics Probenecid (Benemid) Sulfinpyrazone (Anturane) Action Increase uric acid excretion by blocking reabsorption of uric acid Side effects Gastric irritation; patient should take with food. Nursing interventions Use caution when giving with other highly protein-bound drugs. Patient should increase fluid intake to increase uric acid excretion. 27

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